Arylation of halogenated thiophene carboxylate via Suzuki–Miyaura reaction: Anti-bacterial study against clinically isolated extensively drug resistant Escherichia coli sequence type 405 and computational investigation

Mujahid, Aqsa; Rasool, Nasır; Qamar, Muhammad Usman; Zubaır, Muhammad; Ahmad, Fatima; Altaf, Ataf Ali; Akhtar, A.; Shah, Syed Adnan Alı; Alqahtani, Faleh; Alsanea, Sary; Albekairi, Thamer H.; Nasim, Muahammad Jawad; Rasool, Muhammad Fawad; Imran, Imran

doi:10.1016/j.arabjc.2021.103662

Cited by 5 publications

(4 citation statements)

References 38 publications

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“…[29][30][31] Our research team employed SMC coupling to synthesize carboxamides and carboxylate derivatives, which were then tested for their in-vitro anti-bacterial properties against WHO-listed extremely resistant bacterial strains, aiming to identify potential therapeutic candidates. [32][33][34][35] In the present study, both the ESBL producing E. coli and MRSA were resistant to commonly used antibiotics including penicillins, cephalosporins, and beta-lactam inhibitors. The anti-bacterial activity of butyl 2-bromoisonicotinate molecules and its derivatives against ESBL-producing E. coli ST405 and MRSA.…”

Section: Discussionmentioning

confidence: 59%

“…At the same time, the amides behave as a hydrophilic binding site against bacterial enzyme proteins, which may cause death or make static growth, leading to good inhibitory activity. 36 Further, we studied the N, O, and S heterocycles carboxamides like N-(4-bromophenyl)furan-2-carboxamide, 32 2-aryl-4-chlorophenyl-5-arylthiophene-2-carboxylates 34 4-bromo-N-(5-methyl-1H-pyrazol-3-yl) benzamide, 35 N-(4-methylpyridin-2-yl) Thiophene-2-Carboxamide 37 to study the effectiveness of these scaffolds and found effectiveness against different resistant strains of E. coli, A. baumannii, S. enterica, E. cloacae, S. aureus and K. pneumoniae. We found that heterocyclic carboxamides are pivotal in anti-bacterial activities.…”

Section: Discussionmentioning

confidence: 99%

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Synthesis, Anti-Bacterial and Molecular Docking Studies of Arylated Butyl 2-Bromoisonicotinate Against Clinical Isolates of ESBL-Producing Escherichia coli ST405 and Methicillin-Resistant Staphylococcus aureus

Naheed,

Din,

Qamar

et al. 2023

IDR

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Introduction: Global public health concerns include the emergence and spread of methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase Escherichia coli (ESBL-E. coli). These pathogens cause infections that are difficult to treat, which can have fatal outcomes and require lengthy hospital stays. As a result, we created butyl 2-bromoisonicotinate and tested its antibacterial effectiveness against the ESBL-E. coli ST 405 and MRSA pathogens. Natural product discovery is complemented by synthetic compound synthesis because of the latter's potential for superior characteristics, target specificity, scalability, intellectual advantages, and chemical diversity. Because of this, the potential for discovering new medicinal compounds is increased, and the constraints placed on natural sources are overcome. Natural items are tough to obtain since they are hard to isolate and synthesize. Therefore, modern science is actively searching for small molecules as therapeutic agents by applying sustainable techniques that can be commercialized. Methods: Two patients' blood samples were taken, and the BACTEC/Alert system was used to process them. On blood and MacConkey agar, the positive samples were subcultured and incubated aerobically at 37 °C. Using the VITEK 2 compact system, the isolates were subjected to isolate identification and MIC. MLST of the ESBL-E. coli was performed by PCR. Additionally, Fischer esterification was used to create butyl 2-bromoisonicotinate in excellent yields. A commercially available palladium catalyst was then used to arylate the compound, resulting in medium to good yields of arylated butyl 2-bromoisonicotinates. Using the agar well diffusion assay and the micro-broth dilution method, we assessed the in-vitro activities of the synthesized molecules (3, 5a-h) against clinically isolated ESBL-E. coli ST405, and MRSA. A molecular operating environment was used to carry out in silico validation of the synthesized compounds' binding to the active site and to evaluate the stability of their molecular interactions with the target E. coli 2Y2T protein.Results: MRSA and ESBL-producing E. coli were identified as the two clinical isolates. While MRSA was also resistant to betalactam drugs and least resistant to vancomycin, ESBL-producing E. coli belonged to ST405 and was resistant to cephalosporins and sensitive to carbapenems. Good yields of the desired compounds were produced by our effective and economical synthesis. By using a micro-broth dilution assay, the Molecules (3, 5a, and 5d) were most effective against both resistant strains. The Molecules (3, 5a, 5b, and 5d) also displayed good binding energies. Conclusion:The butyl 2-bromoisonicotinate displayed antibacterial efficacy against ESBL-producing E. coli ST405 and MRSA strains. After the in-vivo trial, this substance might offer an alternative therapeutic option.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Synthesis, Anti-Bacterial and Molecular Docking Studies of Arylated Butyl 2-Bromoisonicotinate Against Clinical Isolates of ESBL-Producing Escherichia coli ST405 and Methicillin-Resistant Staphylococcus aureus

Naheed,

Din,

Qamar

et al. 2023

IDR

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“…Additionally, in order to evaluate the efficacy of this stent, we also looked at N, O, and S heterocyclic formamides. Further, we studied the N, O , and S heterocycles carboxamides like 2-aryl-4-chlorophenyl-5-arylthiophene-2-carboxylates 43 N -(4-bromophenyl)furan-2-carboxamide, 37 N -(4-methylpyridin-2-yl) Thiophene-2-Carboxamide 4-bromo- N -(5-methyl-1H-pyrazol-3-yl)benzamide 16 , 44 to study the effectiveness of these scaffolds. The drug is effective against Staphylococcus aureus and Klebsiella pneumoniae , as well as resistant strains of Salmonella enterica, Acinetobacter baumannii, Enterobacter cloacae , and E. coli.…”

Section: Discussionmentioning

confidence: 99%

Facile Synthesis of 5-Bromo-N-Alkylthiophene-2-Sulfonamides and Its Activities Against Clinically Isolated New Delhi Metallo-β-Lactamase Producing Klebsiella pneumoniae ST147

Noreen,

Bilal,

Usman Qamar

et al. 2024

IDR

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“…A proton-motive force drives the efflux pump complex. Due to the significance of the antibacterial properties of pyridyl and carboxamide, which we have previously explored in our research against clinically derived resistant bacteria [ 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Antibacterial Efficacy of N-(4-methylpyridin-2-yl) Thiophene-2-Carboxamide Analogues against Extended-Spectrum-β-Lactamase Producing Clinical Strain of Escherichia coli ST 131

et al. 2023

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Development in the fields of natural-product-derived and synthetic small molecules is in stark contrast to the ongoing demand for novel antimicrobials to treat life-threatening infections caused by extended-spectrum β-lactamase producing Escherichia coli (ESBL E. coli). Therefore, there is an interest in the antibacterial activities of synthesized N-(4-methylpyridin-2-yl) thiophene-2-carboxamides (4a–h) against ESBL-producing E. coli ST131 strains. A blood sample was obtained from a suspected septicemia patient and processed in the Bactec Alert system. The isolate’s identification and antibacterial profile were determined using the VITEK 2® compact system. Multi-locus sequence typing of E. coli was conducted by identifying housekeeping genes, while ESBL phenotype detection was performed according to CLSI guidelines. Additionally, PCR was carried out to detect the blaCTX-M gene molecularly. Moreover, molecular docking studies of synthesized compounds (4a–h) demonstrated the binding pocket residues involved in the active site of the β-lactamase receptor of E. coli. The result confirmed the detection of E. coli ST131 from septicemia patients. The isolates were identified as ESBL producers carrying the blaCTX-M gene, which provided resistance against cephalosporins and beta-lactam inhibitors but sensitivity to carbapenems. Among the compounds tested, 4a and 4c exhibited high activity and demonstrated the best fit and interactions with the binding pocket of the β-lactamase enzyme. Interestingly, the maximum of the docking confirmations binds at a similar pocket region, further strengthening the importance of binding residues. Hence, the in vitro and molecular docking studies reflect the promising antibacterial effects of 4a and 4c compounds.

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Arylation of halogenated thiophene carboxylate via Suzuki–Miyaura reaction: Anti-bacterial study against clinically isolated extensively drug resistant Escherichia coli sequence type 405 and computational investigation

Cited by 5 publications

References 38 publications

Synthesis, Anti-Bacterial and Molecular Docking Studies of Arylated Butyl 2-Bromoisonicotinate Against Clinical Isolates of ESBL-Producing Escherichia coli ST405 and Methicillin-Resistant Staphylococcus aureus

Synthesis, Anti-Bacterial and Molecular Docking Studies of Arylated Butyl 2-Bromoisonicotinate Against Clinical Isolates of ESBL-Producing Escherichia coli ST405 and Methicillin-Resistant Staphylococcus aureus

Facile Synthesis of 5-Bromo-N-Alkylthiophene-2-Sulfonamides and Its Activities Against Clinically Isolated New Delhi Metallo-β-Lactamase Producing Klebsiella pneumoniae ST147

Antibacterial Efficacy of N-(4-methylpyridin-2-yl) Thiophene-2-Carboxamide Analogues against Extended-Spectrum-β-Lactamase Producing Clinical Strain of Escherichia coli ST 131

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